Patent Application
20100207301
1. Field of the Invention
The present invention relates to a method of forming a fine channel using polymer, which can induce an electrostatic attraction, and a method of forming a fine structure using the same, and more particularly, to a method of forming micro/nano channels and a method of forming micro/nano structures using the same, capable of forming structures such as micro/nano-sized channels economically and rapidly and having good biocompatibility.
2. Description of the Related Arts
With the recent advance of micro and nano fluidics for analysis and separation of biomolecules, many processes have been developed which can form micro- or nano-sized channels using soft lithography, e-beam lithography, and nanoimprint lithography, in addition to traditional photolithography. The micro-sized channels can be easily formed using photolithography and soft lithography. However, photolithography is complicated and expensive. In addition, due to the limitation of pattern size, photolithography is unsuitable for patterning line width of 100 nm (1 nm=10−9 m) or below. To solve these problems of photolithography, so-called ‘soft lithography’ has been developed. (“Polymeric Microstructures Formed by Moulding in Capillaries”, Nature (1995), Kim, E. et al., pp. 581-584, and U.S. Pat. No. 6,355,198.) According to soft lithography, a flexible Poly-DiMethylSiloxane (PDMS) mould is spontaneously brought into conformal contact with a substrate, and a prepolymer flows into an empty space between the mould and the substrate due to capillary force. Then, the prepolymer is cured to form patterns.
When PDMS is used, however, the deficiency of physical properties as an elastomer makes it impossible to duplicate a nano structure of 100 nm or less. That is, PDMS-based soft lithography has difficulty in forming nano-sized channels. Also, soft lithography forms structures by inducing conformal contact using wetting properties and elasticity of the mould itself. That is, soft lithography poses serious limitations in that it must use materials with low mechanical modulus and excellent wetting properties.
The resolution limitation of soft lithography can be resolved by the use of e-beam lithography or nanoimprint lithography. However, since the e-beam lithography employs an anodic bonding or a fusion bonding for bonding channels using a high voltage or high temperature, it is difficult to secure channel stability after the bonding. In addition, since heat resistant materials must be used, material limitation is severe. Moreover, since master patterns formed by photolithography or e-beam lithography are used, the manufacturing efficiency is low and the manufacturing cost is very high.
The nanoimprint lithography is economically unbearable because master patterns formed by the e-beam lithography can be used only one time. Also, a heat bonding method depends on fluidity of polymer above the polymer's glass transition temperature during the process of forming channels. Therefore, the size adjustment is difficult. Further, the above-described methods cannot be applied to various processes because the substrate is made of rigid materials such as silicon or glass.
Meanwhile, when the channels are used for bio material analysis, contamination of channel wall with reagent molecules must be solved. SU-8 channels and glass/PDMS channels have been widely used as the channels.
In the case of SU-8 channels, their surface characteristics are unsuitable for analysis of target samples with high accuracy. This is because biomolecules in a flowing stream within the channel adsorb to the channel wall non-specifically. Also, since the channels are bonded at high voltage and high pressure, chips may be damaged.
In the case of the glass/PDMS channels, since the PDMS has many advantages such as flexibility, low cost, transparency, the glass/PDMS channels have been used as channels of biological diagnosis or analysis systems. However, since the channels are bonded by modifying their surfaces using plasma, the durability or channel stability is poor. Also, since the glass/PDMS channels have hydrophobic surfaces, non-selective adsorption of biological species such as cells and proteins within the channels is caused when the glass/PDMS channels are used for a long time. Consequently, the channels are clogged or damaged. Most of all, the above-described methods have problems in that nano-sized channels cannot be formed due to limitations of pattern size.
To prevent non-selective adsorption of biomolecules within the conventional micro channels, a variety of methods have been proposed. As one example, inner surfaces of channels are modified using materials that can prevent non-selective adsorption of biomolecules such as Poly Ethylene Glycol (PEG). This technology was set forth as a self-assembled monolayer. (M. B. Stark, K. Hlmberg, Biotechnol. Bioeng. 1989, 34, 942, and Jon, S. Y.; Seong, J. H.; Khademhosseini, A.; Tran, T. N. T.; Laibinis, P. E.; Langer, R. Langmuir 2003, 19, 9989-9993). This technology will be briefly described below.
First, glass substrate is bonded to a PDMS micro channel. To inhibit inner surfaces of the channels from reacting with biomolecules, a solution dissolved with PEG polymer is flowed into the channels. Then, properties of the glass or PDMS channels are changed. According to this technology, however, it is difficult to continuously maintain the surfaces to have the desired properties. Also, the solution flowing into the channels may cause a secondary pollution. Moreover, this technology is hard to apply to nano-sized channels and the processes are complicated and difficult.
As another method for improving the inner surface properties of the channels, some material that can improve the quality of a PDMS is mixed and channels are then formed. This method can prevent non-selective adsorption of biomolecules compared with channels whose surfaces are not modified, but its efficiency is relatively low and its process is complicated. In addition, all of the existing nano channels cause non-selective adsorption by biological species.
An object of the present invention is to provide a method of forming micro/nano channels using an electrostatic attraction, capable of easily adjusting the size of patterns up to nanometer and preventing non-selective adsorption by biomolecules.
Another object of the present invention is to provide a method of micro/nano structure using the method of forming micro/nano channels.
According to an aspect of the present invention, there is provided a method of forming a fine, irreversibly sealed channel using an electrostatic attraction, including: forming UV curable polymer patterns on a first substrate; sealing the UV curable polymer patterns and a second substrate by an electrostatic attraction, the second substrate including a UV curable polymer layer formed thereon; and forming a channel by irradiating UV light such that UV curable polymer patterns and the UV curable polymer layer sealed together are cross-linked by polymerization.
According to another aspect of the present invention, there is provided a method of forming a fine structure using an electrostatic attraction, including: forming UV curable polymer patterns on a first substrate; contacting the UV curable polymer patterns with a third substrate to reversibly seal the UV curable polymer patterns and the third substrate by an electrostatic attraction on; irradiating UV light on the UV curable polymer patterns reversibly sealed with the third substrate; forming prepolymer patterns on the third substrate by flowing prepolymer between the third substrate and the polymer patterns to which the UV light is irradiated; curing the prepolymer patterns by irradiating UV light thereon; and removing the first substrate with the UV curable polymer patterns from the third substrate with the cured prepolymer patterns.
According to the present invention, any material that can generate an electrostatic attraction may be used without special limitations. The nano-sized channels as well as the micro-sized channels can be formed through the substantially equal processes. Also, the reversible sealing or the irreversible sealing can be freely selected according to the coating of the curable polymer and UV irradiation time. Therefore, the methods of the present invention are very useful to overcome the limitations of the conventional soft lithography, nanoimprint lithography, and e-beam lithography, which require much cost and complicated processes or has limitation in terms of pattern size.
Nano channels can be formed using substrates formed of various materials, in addition to silicon or quartz substrates. Thus, various kinds of substrates can be used according to purposes. Specifically, in the case of a film substrate, it is possible to form reliable fine channels even if stepped polymer patterns are used.
Also, by using the reversible sealing between the substrate and the polymer, good quality of nano structure having no residual layer can be easily formed. Further, by using a transparent substrate and a biocompatible polymer that can generate the electrostatic attraction, fluorescent analysis of materials is easy in analyzing fluid or bio material. Therefore, the present invention can be widely applied to high-efficiency chips, drug delivery system and DNA separation and analysis using nano fluidics. It is to be understood that both the foregoing general description and the following detailed description of the present invention are exemplary and explanatory and are intended to provide further explanation of the invention as claimed.
The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this application, illustrate embodiment(s) of the invention and together with the description serve to explain the principle of the invention. In the drawings:
Hereinafter, a method of forming micro/nano channels using an electrostatic attraction and a method of forming a fine structure using the same according to the preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings. First, the present invention provides a method of forming micro/nano channels using polymer that can generate an electrostatic attraction.
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This embodiment will now be described in detail step by step.
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If the first substrate 10 is formed of a transparent film such as Poly(Ethylene terephthalate (PET), channels formed using the method of the present invention can be suitably used for analysis of biomolecules. However, the present invention is not limited to this material.
The UV curable polymer patterns 20 may be formed using any material that can generate an electrostatic attraction together with the polymer layer and can be cured by UV irradiation or cross-linked with a contacting structure. Examples of the polymer may include poly ethylene glycol (PEG), poly urethane, poly styrene, and poly methyl methacrylate (PMMA). Specifically, if PEG is used, the channels formed using the method of the present invention can prevent pollution due to biomolecules. In further detail, since it is possible to prevent non-selective adsorption with respect to biomolecules contacting the inner surfaces of the channels, the channels can be used in bio chips.
The UV curable polymer patterns 20 can be formed in various methods.
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The UV curable polymer patterns 20 can be formed by another methods.
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According to the method of present invention, the UV curable polymer patterns 20 contact a second substrate 30 where the UV curable polymer layer 40 is formed.
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On the contrary, according to the present invention, any polymer that can induce the electrostatic attraction regardless of wetting properties can be used nano-sized patterns as well as micro-sized patterns can be easily formed according to line width of the mould. Specifically, when the first substrate 10 where the UV curable polymer patterns 20 are formed contacts the polymer layer 40, a negative (−) polarity is induced on the surface of the UV curable polymer patterns 20 and a positive (+) polarity is induced on the opposite surface thereof. Therefore, a conformal contact is formed between the UV curable polymer patterns 20 and the polymer layer 40 due to an instantaneously strong electrostatic attraction.
In this case, it is preferable that a flexible film substrate be used as the first substrate 10 or the second substrate 20 so as to effectively obtain the conformal contact. Such a flexible film substrate includes a PET film. If the cross linkage is performed by the UV irradiation, the conformal contact results in an irreversible sealing. On the contrary, if no UV light is irradiated, a reversible sealing is maintained.
The UV curable polymer layer 40 is formed on the second substrate 30 by spin-coating a UV curable polymer.
Specifically, the UV curable polymer layer 40 is formed by spin-coating the UV curable polymer on the second substrate and irradiating UV light on the spin-coated UV curable polymer.
At this point, in case where a film substrate is used, the UV curable polymer layer 40 and the UV curable polymer patterns 20 can be sealed with a conformal contact even if the UV curable polymer patterns 20 are stepped. Consequently, the reliable channels can be formed.
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The present invention provides a method of easily and economically forming a variety of structures, such as micro/nano-sized patterns, using polymer where charges are formed on their surfaces so that an electrostatic attraction can be generated.
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It is preferable that the bonding force between the prepolymer patterns 70 and the third substrate 30 due to the UV irradiation on the prepolymer patterns 72 be greater than that between the third substrate 60 and the UV curable polymer patterns 20 due to the UV irradiation in
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Next, UV light is irradiated on the pillar-shaped UV curable polymer patterns 20 that is reversibly sealed with the third substrate 60 (see
Also, various kinds of structures can be easily formed by changing the shapes of the UV curable polymer patterns 20 into various shapes other than the linear or pillar shape. If the structures are used in bio chips, the efficiency in the analysis of biomolecules can be remarkably increased. As described above, if using the polymer that can induce the electrostatic attraction, the structures requiring the reversible or irreversible contact can be easily formed through the basically equal processes by changing only the use of UV irradiation, and so on. Also, if adjusting the pattern size of the mould, micro- and nano-sized patterns can be formed through the equal processes.
The present invention will be understood more fully through the exemplary embodiments. However, the embodiments are merely illustrative but not construed as limiting the present invention.
A PEG, which is a biocompatible polymer, was dropped and coated on a silicon mould patterned by a photo lithography. A PET film as a first substrate was covered on the coated PEG and was cured by irradiating UV light for about 20 seconds. Then, the silicon mould was removed to form a first substrate with polymer patterns.
2) Contact of Polymer Patterns and Polymer layer
A PET film was prepared as a second substrate. A PEG was coated on the second substrate by a spin coating process. The spin coating was performed at 2000 RPM for about 20 seconds. Then, the second substrate and the coated PEG are sealed together by irradiating UV light for 10 seconds.
UV light was irradiated for 3 hours so as to irreversibly seal the PEG polymer layer coated on the second substrate with the PEG polymer patterns formed on the first substrate. Due to the UV irradiation, the cross linkage of the polymer was formed and the micro/nano channels were formed.
A first substrate (template) was formed. The first substrate includes linear polymer patterns formed using the process 1) of the first embodiment. Then, the polymer patterns and the Au substrate used as a third substrate were conformally contacted together by an electrostatic attraction. At this point, zeta potential of about −113.55 mV was measured at surfaces of the linear polymer patterns formed on the first substrate (template). Thus, a positive (+) polarity was induced on a surface of the Au substrate opposite to the first substrate, and thus the polymer patterns and the Au substrate were reversibly sealed due to the instantaneous electrostatic attraction. Then, UV light was irradiated for about 3 hours to remove the UV activation groups from the polymer patterns. Through these procedures, a line-shaped space serving as the capillary tube was formed between the polymer patterns and the Au substrate.
The prepolymer was introduced due to the capillary phenomenon by placing the UV curable prepolymer at an entrance of the capillary tube such that the prepolymer could flow into the capillary tube between the polymer patterns and the Au substrate.
1) Reversible Sealing of Polymer Patterns and Third Substrate A first substrate (template) was formed. The first substrate includes polymer patterns having nano-sized pillars. At this point, a silicon mould was patterned to have engraved holes. Then, the polymer patterns with the nano-sized pillars and an Au substrate used as a third substrate were conformally contacted. The polymer patterns and the Au substrate were reversibly sealed due to the instantaneous electrostatic attraction. Then, UV light was irradiated for about 3 hours to remove the UV activation groups from the polymer patterns. Through these procedures, a space between the pillars was formed between the polymer patterns and the Au substrate. The space serves as the capillary tube.
Then, the prepolymer was introduced due to the capillary phenomenon by placing the UV curable prepolymer at an entrance of the capillary tube such that the prepolymer could flow into the capillary tube between the polymer patterns and the Au substrate.
UV light was irradiated for about 5 minutes so as to cure the prepolymer introduced into the capillary tube. Then, the template was removed to form polymer patterns with nanowell exposing the third substrate.
That is, it can be seen from
According to the present invention, any material that can generate an electrostatic attraction may be used without special limitations. The nano-sized channels as well as the micro-sized channels can be formed through the substantially equal processes. Also, the reversible sealing or the irreversible sealing can be freely selected according to the coating of the curable polymer and UV irradiation time. Therefore, the methods of the present invention are very useful to overcome the limitations of the conventional soft lithography, nanoimprint lithography, and e-beam lithography, which require much cost and complicated processes or has limitation in terms of pattern size.
Nano channels can be formed using substrates formed of various materials, in addition to silicon or quartz substrates. Thus, various kinds of substrates can be used according to purposes. Specifically, in the case of a film substrate, it is possible to form reliable fine channels even if stepped polymer patterns are used.
Also, if using the reversible sealing between the substrate and the polymer, good quality of nano structure having no residual layer can be easily formed. Further, Moreover, if using a transparent substrate and a biocompatible polymer that can generate the electrostatic attraction, fluorometric analysis of materials is easy in analyzing fluid or bio material. Therefore, the present invention can be widely applied to high-efficiency chips, drug delivery system and DNA separation and analysis using nano fluidics.
